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Hypoxia‐inducible factor (HIF) plays a critical role in the mechanisms that allow cells to adapt to various oxygen levels in the environment. Specifically, HIF‐1⍺ has shown to be widely involved in cellular repair, survival, and energy metabolism. HIF‐1⍺ has also been found in increased levels in cancer cells, highlighting the importance of balance in the hypoxic response. Promoting HIF‐1⍺ activity as a potential therapy for degenerative diseases and inhibiting HIF‐1⍺ as a therapy for pathologies with overactive cell proliferation are actively being explored. Digoxin and metformin, HIF‐1⍺ inhibitors, and deferoxamine and ⍺‐ketoglutarate analogues, HIF‐1⍺ activators, are being studied for application in age‐related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. However, these same medications have retinal toxicities that must be assessed before implementation of therapeutic care. Herein, we highlight the duality of therapeutic and toxic potential of HIF‐1⍺ that must be carefully assessed prior to its clinical application in retinal disorders. [ABSTRACT FROM AUTHOR]

Introduction: Leber congenital amaurosis (LCA) type 2, due to disease‐causing variants in RPE65, is characterized by severe visual loss in early infancy. Current treatments include voretigene neparvovec‐rzyl (VN) for RPE65‐associated LCA. Herein, we present the long‐term follow‐up of a patient treated with VN using quantitative autofluorescence (488 nm excitation). Case Report: A 9‐year‐old girl with a diagnosis of LCA with biallelic variants in RPE65 presented for evaluation. The patient underwent VN treatment at the age of 11. The patient returned to clinic at age of 19 at which time imaging revealed evidence of chorioretinal atrophy. Quantitative autofluorescence performed prior to gene therapy and at 6‐ and 8‐year follow‐up revealed a central area of fundus autofluorescence. Discussion This case report demonstrates acquisition of fundus autofluorescence at 6‐ and 8‐year follow‐up despite the development of chorioretinal atrophy. [ABSTRACT FROM AUTHOR]